Faculty Bibliography
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person:trasal01 or ghassa01
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441
Maternal C-Reactive Protein Concentration in Early Pregnancy and Child Autistic Traits in the General Population
BACKGROUND: Exposure to elevated levels of inflammatory markers during pregnancy has been suggested as possible aetiologic factor in the occurrence of autism spectrum disorder (ASD). In this study, we investigated the prospective relation between maternal C-reactive protein (CRP) during early pregnancy and children's autistic traits in the general population. METHODS: In a large population-based cohort in the Netherlands, we measured maternal CRP levels before 18 weeks of gestation (N = 4165). Parents reported on their children's autistic traits at age 6 years using the Social Responsiveness Scale, and the Pervasive Developmental Problem scale. Regression models were used to examine the relation between maternal CRP levels and autistic traits in children. RESULTS: Compared with the reference group (CRP < 2.3 mg/L), elevated levels of CRP (>7.8 mg/L) in pregnant women were associated with higher Social Responsiveness Scale scores in children [beta = 0.055, 95% confidence interval (CI) 0.033, 0.078]; however, the effect was strongly attenuated after adjustment for several socioeconomic factors and in particular by maternal health-related factors including body mass index (fully adjusted model beta = 0.018, 95% CI -0.005, 0.042). We found no relation between maternal CRP levels and pervasive developmental problem. CONCLUSIONS: Our results suggest that the association between elevated levels of maternal CRP in pregnancy and autistic traits in children is confounded by maternal health-related and socioeconomic factors. Further studies are needed to explore whether other maternal inflammatory markers during pregnancy, as a response to maternal inflammation, are associated with the development of autistic traits in the offspring.
PMCID:4751036
PMID: 26860445
ISSN: 1365-3016
CID: 2117822
Examining Infertility Treatment and Early Childhood Development in the Upstate KIDS Study
IMPORTANCE: An increasing percentage of births are conceived with assisted reproductive technology (ART) and other infertility treatment. Despite findings that such treatments may be associated with diminished gestation and birth size, scarce data exist regarding infertility treatments and children's development in the United States. OBJECTIVE: To assess the use and type of infertility treatment in relation to children's development through age 36 months. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (conducted 2008-2014) that sampled based on infertility treatment and plurality. Included in the study were infants born between 2008 and 2010 in New York state (excluding New York City) whose parents completed developmental screening instruments through 36 months of age. A total of 4824 mothers (97% of 4989) completed 1 or more developmental screening instruments for 5841 children, including 1830 conceived with infertility treatment and 2074 twins. EXPOSURES: Maternal self-report of any infertility treatment was further categorized into ART and ovulation induction/intrauterine insemination. Assisted reproductive technology use was previously validated by linkage with the Society for Assisted Reproductive Technology-Clinical Outcome Reporting System. MAIN OUTCOMES AND MEASURES: Five developmental domains (fine motor, gross motor, communication, personal-social functioning, and problem-solving ability), as measured by the parental completion of the Ages and Stages Questionnaires at 4, 8, 12, 18, 24, 30, and 36 months of age. Generalized linear mixed modeling techniques estimated adjusted odds ratios (aORs) and 95% CIs for use and type of infertility treatment in relation to failing a developmental domain. Data were stratified by plurality and weighted for the sampling scheme. RESULTS: There were 1422 mothers (29.5%; mean [SD], age, 34.1 [5.2] years) who underwent infertility treatment. Infertility treatment was not associated with risk of their children failing any developmental domain (aOR, 1.33; 95% CI, 0.94-1.89). Assisted reproductive technology was associated with increased risk for failing any developmental domain but only when singletons and twins were evaluated together (aOR, 1.81; 95% CI, 1.21-2.72). Adjustment for birth weight further attenuated this estimate (aOR, 1.26; 95% CI, 0.82-1.93). After stratifying by plurality, type of treatment also was not significantly associated with failing any developmental domain for ovulation induction/intrauterine insemination (aOR, 1.00; 95% CI, 0.57-1.77 for singletons and aOR, 1.30; 95% CI, 0.76-2.21 for twins) or ART (aOR, 1.38; 95% CI, 0.78-2.43 for singletons and aOR, 1.58; 95% CI, 0.94-2.65 for twins). CONCLUSIONS AND RELEVANCE: After considering plurality, children's development through age 3 years was similar irrespective of infertility treatment or specific type. To our knowledge, these findings are among the first to focus on non-ART treatments in the United States.
PMCID:5000851
PMID: 26746435
ISSN: 2168-6211
CID: 2117842
Urinary polycyclic aromatic hydrocarbons and measures of oxidative stress, inflammation and renal function in adolescents: NHANES 2003-2008
OBJECTIVE: Recent evidence has suggested that polycyclic aromatic hydrocarbons (PAHs) may contribute to cardiometabolic and kidney dysfunction by increasing oxidative stress, but little is known about impacts in childhood. STUDY DESIGN: We performed cross-sectional analyses of 660 adolescents aged 12-19 years in the 2003-2008 National Health and Nutrition Examination Survey (NHANES), using levels of 10 monohydroxylated urinary PAH metabolites as our exposure. Our primary outcomes of interest were biomarkers of oxidative stress and renal function, including estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (ACR), insulin resistance, and serum uric acid, gamma glutamyl transferase (GGT) and C-reactive protein (CRP). RESULTS: We observed statistically significant associations between PAH metabolites and levels of serum GGT, CRP, uric acid and eGFR. Each 100% increase in 2-hydroxyphenanthrene was related to a 3.36% increase in uric acid (95% CI: 0.338-6.372; p=0.032), a 3.86% increase in GGT (95% CI: 1.361-6.362; p=0.005) and a 16.78% increase in CRP (95% CI: 1.848-31.689; p=0.029). Each 100% increase in 4-hydroxyphenanthrene was associated with a 6.18% increase in GGT (95% CI: 4.064-8.301; p<0.001) and a 13.66% increase in CRP (95% CI: 2.764-24.564; p=0.017). Each 100% increase in 9-hydroxyfluorene was associated with a 2.58% increase in GGT (95% CI: 0.389-4776; p=0.024). Each 100% increase in 3-hydroxyphenanthrene was associated with a 2.66% decrease in eGFR (95% CI: -4.979 to -0.331; p=0.028). CONCLUSIONS: Urinary PAH metabolites were associated with serum uric acid, GGT and CRP, suggesting possible impacts on cardiometabolic and kidney function in adolescents. Prospective work is needed to investigate the potential long-term health consequences of these findings.
PMCID:4679617
PMID: 26610293
ISSN: 1096-0953
CID: 1857042
Air Pollution Exposure during Pregnancy and Childhood Autistic Traits in Four European Population-Based Cohort Studies: The ESCAPE Project
BACKGROUND: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. OBJECTIVES: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. METHODS: Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of
PMCID:4710593
PMID: 26068947
ISSN: 1552-9924
CID: 2117882
International journal of environmental research & public health. 2015:13(1).DOI: 10.3390/ijerph13010080
Improving Knowledge about Children's Environmental Health in Northwest China
The main purpose of this study was to identify policy maker opinions and attitudes towards children's environmental health (CEH), potential barriers to child-specific protective legislation and implementation in northwest China, and evaluate knowledge and attitudes about CEH before and after an educational conference. We conducted seventy-two interviews with regional officials, researchers and non-governmental organization representatives from five provinces, and surveyed participants (forty-seven) before and after an educational conference in northwest China about CEH. Interviews identified general consensus among participants of the adverse effects of air pollution on children, yet few participants knew of policies to protect them. Barriers identified included limited funding and enforcement, weak regional governments and absence of child-specific policy-making. After the conference, substantially greater self-efficacy was identified for lead, mercury, air pollution and polychlorinated biphenyls (+0.57-0.72 on a 1-5 Likert scale, p = 0.002-0.013), and the scientific knowledge for the role of environment in children's health (+0.58, p = 0.015), and health care provider control (+0.52, p = 0.025) were rated more strongly. We conclude that policy makers in Northwest China appreciate that children are uniquely vulnerable, though additional regulations are needed to account for that vulnerability. Further research should examine effectiveness of the intervention on a larger scale and scope, and evaluate the usefulness of such interventions in translating research into improved care/reduced exposure to environmental hazards.
PMCID:4730471
PMID: 26712775
ISSN: 1660-4601
CID: 1894472
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57.2% (95% uncertainty interval [UI] 55.8-58.5) of deaths and 41.6% (40.1-43.0) of DALYs. Risks quantified account for 87.9% (86.5-89.3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11.3 million deaths and 241.4 million DALYs, high systolic blood pressure for 10.4 million deaths and 208.1 million DALYs, child and maternal malnutrition for 1.7 million deaths and 176.9 million DALYs, tobacco smoke for 6.1 million deaths and 143.5 million DALYs, air pollution for 5.5 million deaths and 141.5 million DALYs, and high BMI for 4.4 million deaths and 134.0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.
PMCID:4685753
PMID: 26364544
ISSN: 1474-547x
CID: 2033272
Melamine Nephrotoxicity is Mediated by Hyperuricemia
OBJECTIVE: We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo). METHODS: Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition. RESULTS: Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones. CONCLUSION: Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.
PMID: 26777910
ISSN: 0895-3988
CID: 1921332
Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents
BACKGROUND: Perfluoroalkyl acids are synthetic compounds widely used in industrial and commercial applications. Laboratory studies suggest that these persistent and bioaccumulative chemicals produce oxidant stress and damage glomerular endothelial cells, raising concern regarding the impact of these compounds on renal function. METHODS: We performed cross-sectional analyses of data 1960 participants aged 12-19 years of the 2003-2010 National Health and Nutrition Examination Surveys. PFAA exposure was assessed using levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid, and perfluorohexane sulfonic acid. Primary study outcomes were estimated glomerular filtration rate (eGFR) and serum uric acid. RESULTS: While adjusting for demographics, cotinine, prehypertension, insulin resistance, body mass index, and hypercholesterolemia, adolescents in the highest PFOA and PFOS quartile had a lower eGFR, 6.84 mL/min/1.73 m2 (95 % CI: 2.19 to 11.48) and 9.69 mL/min/1.73 m2 (95 % CI: -4.59 to 14.78), respectively, compared to the lowest quartile. Highest PFOA and PFOS quartiles were also associated with 0.21 mg/dL (95 % CI: 0.056 to 0.37) and 0.19 mg/dL (95 % CI: 0.032 to 0.34) increases in uric acid, respectively. CONCLUSIONS: PFAAs are associated with a reduction in kidney function and increased uric acid levels in otherwise healthy adolescents. Reverse causation and residual confounding could explain the results. Our study results confirm and amplify previous findings, though longitudinal studies examining prenatal and childhood biomarkers in relationship with robust measures of childhood renal function are needed.
PMCID:4654837
PMID: 26590127
ISSN: 1476-069x
CID: 1848912
A Comparison of Ambulatory Care Sensitive Hospitalizations Among Children With and Without Autism Spectrum Disorder
OBJECTIVE:To compare the prevalence of hospitalizations for ambulatory care sensitive conditions (ACSC) in children with and without autism spectrum disorder (ASD) and to compare inpatient health care utilization (total charges and length of stay) for the same conditions in children with and without ASD. METHODS:The 2009 Kids' Inpatient Database was used to examine hospitalizations for ACSC in children within 3 cohorts: those with ASD, those with chronic conditions (CC) without ASD, and those with no CC. RESULTS:The proportion of hospitalizations for ACSC in the ASD cohort was 55.9%, compared with 28.2% in the CC cohort and 22.9% in the no-CC cohort (PÂ <Â .001). Hospitalized children with ASD were more likely to be admitted for a mental health condition, epilepsy, constipation, pneumonia, dehydration, vaccine-preventable diseases, underweight, and nutritional deficiencies compared with the no-CC cohort. Compared with the CC cohort, the ASD cohort was more likely to be admitted for mental health conditions, epilepsy, constipation, dehydration, and underweight. Hospitalized children with ASD admitted for mental health conditions had significantly higher total charges and longer LOS compared with the other 2 cohorts. CONCLUSIONS:The proportion of potentially preventable hospitalizations is higher in hospitalized children with ASD compared with children without ASD. These data underscore the need to improve outpatient care of children with ASD, especially in the areas of mental health care and seizure management. Future research should focus on understanding the reasons for increased inpatient health care utilization in children with ASD admitted for mental health conditions.
PMID: 26547543
ISSN: 1876-2867
CID: 3502412
DHA in Pregnant and Lactating Women from Coastland, Lakeland, and Inland Areas of China: Results of a DHA Evaluation in Women (DEW) Study
Few studies have examined docosahexaenoic acid (DHA) in pregnant and lactating women in developing countries like China, where DHA-enriched supplements are increasingly popular. We aimed to assess the DHA status among Chinese pregnant and lactating women residing areas differing in the availability of aquatic products. In total, 1211 women in mid-pregnancy (17 +/- 2 weeks), late pregnancy (39 +/- 2 weeks), or lactation (42 +/- 7 days) were enrolled from Weihai (coastland), Yueyang (lakeland), and Baotou (inland) city, with approximately 135 women in each participant group by region. DHA concentrations were measured using capillary gas chromatography, and are reported as weight percent of total fatty acids. Mean plasma DHA concentrations were higher in coastland (mid-pregnancy 3.19%, late pregnancy 2.54%, lactation 2.24%) and lakeland women (2.45%, 1.95%, 2.26%) than inland women (2.25%, 1.67%, 1.68%) (p values < 0.001). Similar differences were observed for erythrocyte DHA. We conclude that DHA concentrations of Chinese pregnant and lactating women are higher in coastland and lakeland regions than in inland areas. DHA status in the study population appears to be stronger than populations from other countries studied to date.
PMCID:4632448
PMID: 26506380
ISSN: 2072-6643
CID: 1816822
